We propose to continue studies of the pathogenesis of immune complex nephritis using two approaches. First, we will study the role of altered glomerular permeability and immune aggregate size on localization within glomeruli of defined immune aggregates. To alter glomerular permeability, we will use a model developed by us of proteinuria induced by infusion of the polycation hexadimethrine. Proteinuria and altered glomerular permeability can be confined to one kidney of a rabbit by infusion of hexadimethrine into the left renal artery, with systemic infusion of neutralizing heparin. Defined oligomers of IgG will be produced by cross-linking with the bifunctional agent dimethylsuberimidate. Second, we will continue studies of the role of monocytes and cell-mediated immunity in acute bovine albumin (BSA)-induced serum sickness nephritis in rabbits. We have previously demonstrated that monocytes account for most of the acute glomerular hypercellularity in this model. We propose to deplete monocytes by intraperitoneal injection of carrageenan, a monocyte toxin, and observe the effects on glomerular hypercellularity, glomerular proliferative response and proteinuria. Further, we propose to document the time course of reactivity to BSA of peripheral blood lymphocytes in this model, and relate this correlate of cell-mediated immunity to glomerular lesions and proteinuria.